Effect of oestradiol on dopamine receptors and protein kinase C activity in the rat pituitary: binding of oestradiol to pituitary membranes.
Oestradiol exerts an important modulatory influence on the release of prolactin which is accomplished partly through disruption of the inhibitory influence of dopamine. We have focused on the status of the anterior pituitary D2 dopamine receptor in female rats treated chronically with oestradiol or progesterone. A direct membrane effect of these steroids on the dopamine system was also investigated in vitro. Both steroids affected the status of the D2 receptor, oestradiol decreasing the number of sites in vitro and progesterone increasing it both in vitro and in vivo. The in vitro studies demonstrated that these steroids exert a direct membrane effect on the D2 receptor. These results correlated with an in vitro short-term physiological effect of oestradiol and progesterone on the dopaminergic inhibition of prolactin release, oestradiol decreasing it while progesterone had the opposite effect. Binding studies with [3H] oestradiol on pituitary membranes revealed a site for oestradiol of high affinity and low capacity, indicating that oestradiol's membrane effects could be mediated by a specific receptor. In vivo treatment with oestradiol also induces proliferation of prolactin-secreting cells (lactotrophs). We focused on the effect of oestradiol on protein kinase C activity, which is involved in both secretion and proliferation. In female rats treated with oestradiol total protein kinase C activity was increased by 74% (particulate 90%, soluble 71%) in comparison with controls. This effect was reversed by concomitant treatment with a dopamine agonist. Thus in the pituitary oestradiol and progesterone affect the characteristics of membrane components that are implicated in the physiological control of the cell. Whether these effects are post-transcriptional only or are also mediated through direct membrane mechanisms needs further investigation.
Joubert-Bression
D
D
INSERM U 223, Faculté de Médecine Pitié-Salpêtrière, Paris, France.
Brandi
A M
AM
Birman
P
P
Peillon
F
F
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D010902:Pituitary Gland / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011959:Receptors, Estradiol / Q000187:drug effects* / Q000502:physiology
D011959:Receptors, Estradiol; D004958:Estradiol; D011493:Protein Kinase C